CDC Finds Causal Relationship Between Zika Virus, Birth Defects

It has long been suspected that Zika virus can pass from mother to child and lead to severe birth defects. On April 13, the CDC published a special report(www.nejm.org) in the New England Journal of Medicine that concluded there is a solid causal relationship between prenatal Zika virus infection and microcephaly and other serious brain anomalies.

In the report, titled "Zika Virus and Birth Defects -- Reviewing the Evidence for Causality," researchers noted that evidence supporting this causal relationship included Zika virus infection during prenatal development that was consistent with the defects observed. They also found a "specific, rare phenotype involving microcephaly and associated brain anomalies in fetuses or infants with presumed or confirmed congenital Zika virus infection." In addition, data strongly supported biologic plausibility -- including through identifying Zika virus in the brain tissue of affected fetuses and infants.

"Given the recognition of this causal relationship, we need to intensify our efforts toward the prevention of adverse outcomes caused by congenital Zika virus infection," the report said.

Data was analyzed using Shepard's criteria for proof of human teratology and the Bradford Hill criteria as framework.

Story highlights

On April 13, the CDC published a special report that found a causal relationship between prenatal Zika virus infection and microcephaly and other serious brain anomalies.

On April 15, the CDC released a Morbidity and Mortality Weekly Report focusing on a case of Zika virus transmission through sexual contact between a male traveler who returned from Venezuela and his male non-traveling partner.

To understand more about Zika virus infection during pregnancy and congenital Zika virus infection, the CDC has established the U.S. Zika Pregnancy Registry.

"Also supportive of a causal relationship is the absence of an alternative explanation; despite the extensive consideration of possible causes, researchers have been unable to identify alternative hypotheses that could explain the increase in cases of microcephaly that were observed first in Brazil and then retrospectively in French Polynesia and now in preliminary reports that are being investigated in Colombia," the report said.

However, researchers also noted that many elements critical to the prevention effort still need to be figured out, including the spectrum of defects caused by prenatal Zika virus infection, the degree of relative and absolute risks of adverse outcomes among fetuses whose mothers were infected at different times during pregnancy and factors that might affect a woman's risk of adverse pregnancy or birth outcomes.

"Addressing these questions will improve our ability to reduce the burden of the effects of Zika virus infection during pregnancy," the report said.

Male-to-male Sexual Transmission

On April 15, the CDC released a Morbidity and Mortality Weekly Report (MMWR)(www.cdc.gov) that focused on a case of Zika virus transmission through sexual contact between a male traveler (patient A) who returned to Dallas from Venezuela, which is an area of active Zika virus transmission, and his male non-traveling partner (patient B).

Dallas County Health and Human Services led the initial investigation back in January using epidemiology, laboratory findings and environmental research. The case established for the first time that Zika virus can be transmitted through anal sex, as well as vaginal sex.

Plaque-reduction neutralization tests indicated that patient A had been infected with Zika virus and/or dengue virus serotype 1, but that patient B had been infected only with Zika virus.

Reverse transcription-polymerase chain reaction (RT-PCR) testing of semen collected 17 and 24 days after illness onset was equivocal for patient A and negative for patient B.

In addition to this case, the CDC said at least five other cases of sexually transmitted Zika virus infection have been supported by laboratory evidence and reported in published literature. All of these cases were male-to-female transmissions involving vaginal sex.

The MMWR said studies are ongoing to investigate seminal shedding of infection-competent Zika virus, including its incidence, pattern (e.g., intermittent shedding or a steady decay) and duration.

At the time of Dallas-based patient B's clinical presentation, there had only been one published report that described testing semen from a man with Zika virus infection; two additional studies have since examined Zika infection in semen.

According to the CDC, Zika virus has been detected by RT-PCR and isolated in culture from the semen of two men at least two weeks after onset of illnesses and possibly up to 10 weeks after illness in one of these cases. Another report(wwwnc.cdc.gov) described Zika virus detection in semen by RT-PCR 62 days after illness onset, but a culture was not performed in this case.

Notably, all men in the five case reports and the three semen studies, as well as patient A, experienced symptomatic illness.

CDC Zika Pregnancy Registry

To better understand Zika virus infection during pregnancy and congenital Zika virus infection, the CDC has established the U.S. Zika Pregnancy Registry. Physicians are encouraged to participate in the registry by reporting any laboratory-backed positive cases of Zika virus infection in pregnant patients or infants later born to these patients to their state, tribal, local or territorial health department, or directly to the CDC registry staff if asked to do so by health officials.

The data collected through this registry will be used to update recommendations for clinical care, to prepare services for pregnant women and families affected by Zika virus and to improve prevention of Zika virus infection during pregnancy.